Monoclonal antibodies have proved to be important reagents for the study of rotavirus antigens. Several monoclonal antibodies have been adapted in our laboratory for use in an epitope-blocking immunoassay to analyze antigenic site-specific antibody responses. This assay has been applied to the analysis of sera from various sources including rotavirus vaccine trials and human volunteer and animal studies in an attempt to better understand the development of immunity in the host and identify correlates of resistance to rotavirus illness. Monoclonal antibodies are also vital in identification of serotypes of rotavirus strains circulating in the community during rotavirus vaccine trials. These studies are providing critical information on the epidemiology of rotavirus serotypes and the role of serotype-specific immunity induced by rotavirus vaccine candidates. Analysis of sera of infant vaccinees who developed rotavirus illness during post-immunization surveillance (i.e., "vaccine failures") indicated that failure of vaccinees to develop neutralizing neutralization epitope blocking antibodies to the illness strain was a major correlate of susceptibility to the illness producing rotavirus. Further study of adult volunteers who were challenged with a virulent human serotype 1 rotavirus indicated that resistance to rotavirus infection and diarrhea was strongly associated with antibodies to a serotype 1 or serotype 3 neutralization epitope that maps to amino acid 94 of the outer capsid protein VP7.